The extent of callus formation about a bone fracture depends on the rigidity of fracture fixation. The mechanism that converts the mechanical stimulus into the biologic response is unknown. On the basis of existing literature, an attempt has been made to define a model that explains this mechanobiologic transduction. Once integrity of the bone has been disrupted, a sequence of biochemical and cellular events commences that induces inflammatory reactions. Messengers (e.g., metabolites of the clotting or complement system, eicosanoids, or growth factors) are released or activated. They control the migration, proliferation, and protein synthesis of cells that are essential for angiogenesis and connective tissue formation. The key component in this inflammatory sequence seems to be the macrophage. Growth factors (e.g., released by macrophages) stimulate endothelial cells to form capillaries and mesenchymal cells to synthesize their matrix. In mechanically neutral areas, the fracture cavity is revascularized and osteoblasts proliferate and form bone. In mechanically instable fracture areas, spreading capillaries are disrupted by shear forces. In these areas, therefore, the milieu becomes hypoxic again. This milieu seems to support the differentiation of chondrocytes that stabilize the fracture by cartilage formation. If the strength of repair tissue is surpassed, the disrupture of the repair tissue triggers the mechanisms of inflammation again and additional cells immigrate and proliferate. Their protein synthesis increases repair callus. The increase of callus formation, however, stops when the tissue is capable of resisting motion. Links to the callus formation in osteitis are shown.